A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF: a multicenter randomized non-inferiority trial.

STUDY QUESTION: In subfertile women with poor ovarian reserve undergoing IVF does a mild ovarian stimulation strategy lead to comparable ongoing pregnancy rates in comparison to a conventional ovarian stimulation strategy? SUMMARY ANSWER: A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF leads to similar ongoing pregnancy rates as a conventional ovarian stimulation strategy. WHAT IS KNOWN ALREADY: Women diagnosed with poor ovarian reserve are treated with a conventional ovarian stimulation strategy consisting of high-dose gonadotropins and pituitary downregulation with a long mid-luteal start GnRH-agonist protocol. Previous studies comparing a conventional strategy with a mild ovarian stimulation strategy consisting of low-dose gonadotropins and pituitary downregulation with a GnRH-antagonist have been under powered and their effectiveness is inconclusive. STUDY DESIGN, SIZE, DURATION: This open label multicenter randomized trial was designed to compare one cycle of a mild ovarian stimulation strategy consisting of low-dose gonadotropins (150 IU FSH) and pituitary downregulation with a GnRH-antagonist to one cycle of a conventional ovarian stimulation strategy consisting of high-dose gonadotropins (450 IU HMG) and pituitary downregulation with a long mid-luteal GnRH-agonist in women of advanced maternal age and/or women with poor ovarian reserve undergoing IVF between May 2011 and April 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Couples seeking infertility treatment were eligible if they fulfilled the following inclusion criteria: female age ≥35 years, a raised basal FSH level >10 IU/ml irrespective of age, a low antral follicular count of ≤5 follicles or poor ovarian response or cycle cancellation during a previous IVF cycle irrespective of age. The primary outcome was ongoing pregnancy rate per woman randomized. Analyses were on an intention-to-treat basis. We randomly assigned 195 women to the mild ovarian stimulation strategy and 199 women to the conventional ovarian stimulation strategy. MAIN RESULTS AND THE ROLE OF CHANCE: Ongoing pregnancy rate was 12.8% (25/195) for mild ovarian stimulation versus 13.6% (27/199) for conventional ovarian stimulation leading to a risk ratio of 0.95 (95% CI: 0.57-1.57), representing an absolute difference of -0.7% (95% CI: -7.4 to 5.9). This 95% CI does not extend below the predefined threshold of 10% for inferiority. The duration of ovarian stimulation was significantly lower in the mild ovarian stimulation strategy than in the conventional ovarian stimulation strategy (mean difference -1.2 days, 95% CI: -1.88 to -0.62). Also, a significantly lower amount of gonadotropins was used in the mild simulation strategy, with a mean difference of 3135 IU (95% CI: -3331 to -2940). LIMITATIONS, REASONS FOR CAUTION: A limitation of our study was the lack of data concerning the cryopreservation of surplus embryos, so we are not informed on cumulative pregnancy rates. Another limitation is that we were not able to follow up on the ongoing pregnancies in all centers, so we are not informed on live birth rates. WIDER IMPLICATIONS OF THE FINDINGS: The results are directly applicable in daily clinical practice and may lead to considerable cost savings as high dosages of gonadotropins are not necessary in women with poor ovarian reserve undergoing IVF. A health economic analysis of our data planned to test the hypothesis that mild ovarian stimulation strategy is more cost-effective than the conventional ovarian stimulation strategy is underway. STUDY FUNDING/COMPETING INTERESTS: This study was supported by NUFFIC scholarship (the Netherlands) and STDF short-term fellowship (Egypt). TRIAL REGISTRATION NUMBER: NTR2788 (Trialregister.nl). TRIAL REGISTER DATE: 01 March 2011. DATE OF FIRST PATIENT'S ENROLMENT: May 2011.

Gonadotrophins for idiopathic male factor subfertility.

BACKGROUND: Male factor infertility accounts for 50% of all infertility. The treatment of idiopathic male infertility is empirical. Urinary, purified, and recombinant gonadotrophins have been used to improve sperm parameters in idiopathic male infertility with the goal of increasing pregnancy rates. Research addressing pregnancy rates in partners of men treated with gonadotrophins has had conflicting results and needs to be analysed. OBJECTIVES: To determine the effectiveness of gonadotrophin administration in men with idiopathic subfertility in improving spontaneous pregnancy rate and in assisted reproductive technique cycles. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (31 May 2007), the Cochrane Central Register of Controlled Trials (The Cochrane Library, issue 2, 2007), MEDLINE (1966 to May 2007), EMBASE and Biological Abstracts (1980 to Week 21 2007). Searches were not limited by language. The bibliographies of included, excluded trials and abstracts of major meetings were searched for additional trials. Authors and pharmaceutical companies were contacted for missing and unpublished data. SELECTION CRITERIA: Truly randomised controlled trials where gonadotrophins were administered for the treatment of idiopathic male subfertility with reporting of pregnancy rates were included in the review. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. We analysed data regarding pregnancy occurring within three months after gonadotrophin therapy. MAIN RESULTS: Four RCTs with 278 participants were included in the analysis. None of the studies had an adequate sample size and they had variable follow-up periods. None of the studies reported live birth or miscarriage rates. Compared to placebo or no treatment, gonadotrophins showed a significantly higher pregnancy rate per couple randomized within three months of completing therapy ( OR 4.17, 95% CI 1.30 to 7.09). AUTHORS' CONCLUSIONS: The number of trials and participants is insufficient to draw final conclusions. A large multicenter study with adequate power is needed.

Gonadotrophin-releasing hormone antagonists for assisted conception.

BACKGROUND: Gonadotrophin-releasing hormone antagonists produce immediate suppression of gonadotrophin secretion, hence, they can be given after starting gonadotrophin administration. This has resulted in dramatic reduction in the duration of treatment cycle. Two different regimes have been described. The multiple-dose protocol involves the administration of 0.25 mg cetrorelix (or ganirelix) daily from day six to seven of stimulation, or when the leading follicle is 14 to15 mm, until human chorionic gonadotrophin (HCG) administration and the single-dose protocol involves the single administration of 3 mg cetrorelix on day seven to eight of stimulation. Assuming comparable clinical outcome, these benefits would justify a change from the standard long protocol of GnRH agonists to the new GnRH antagonist regimens. OBJECTIVES: To evaluate the evidence regarding the efficacy of gonadotrophin-releasing hormone (GnRH) antagonists with the standard long protocol of GnRH agonists for controlled ovarian hyperstimulation in assisted conception. SEARCH STRATEGY: We searched Cochrane Menstrual Disorders and Subfertility Group's Specialised Register, MEDLINE and EMBASE databases from 1987 to February 2006, and handsearched bibliographies of relevant publications and reviews, and abstracts of scientific meetings. We also contacted manufacturers in the field. SELECTION CRITERIA: Randomized controlled studies comparing different protocols of GnRH antagonists with GnRH agonists in assisted conception cycles were included in this review. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. If relevant data were missing or unclear, the authors have been consulted MAIN RESULTS: Twenty seven RCTs comparing the GnRH antagonist to the long protocol of GnRH agonist fulfilled the inclusion criteria. Clinical pregnancy rate was significantly lower in the antagonist group. (OR = 0.84, 95% CI = 0.72 - 0.97). The ongoing pregnancy/ live-birth rate showed the same significant lower pregnancy in the antagonist group (P = 0.03; OR 0.82, 95% CI 0.69 to 0.98).However, there was statistically significant reduction in incidence of severe OHSS with antagonist protocol. The relative risk ratio was (P = 0.01; RR 0.61, 95% CI 0.42 to 0.89). In addition, interventions to prevent OHSS (e.g. coasting, cycle cancellation) were administered more frequently in the agonist group (P = 0.03; OR 0.44, 95% CI 0.21 to 0.93). AUTHORS' CONCLUSIONS: GnRH antagonist protocol is a short and simple protocol with good clinical outcome with significant reduction in incidence of severe ovarian hyperstimulation syndrome and amount of gonadotrophins but the lower pregnancy rate compared to the GnRH agonist long protocol necessitates counseling subfertile couples before recommending change from GnRH agonist to antagonist..

Levonorgestrel-releasing intrauterine device (LNG-IUD) for symptomatic endometriosis following surgery.

BACKGROUND: Various options exist for treating endometriosis, including ovarian suppression therapy, surgical treatment or a combination of these strategies. Surgical treatment of endometriosis sets out to remove visible areas of endometriosis and restore anatomy by division of adhesions. The aim of medical therapy is to inhibit growth of endometriotic implants by suppression of ovarian steroids and induction of a hypo-estrogenic state. Postoperative treatment with a hormone-releasing intrauterine system, using levonorgestrel (LNG-IUS), has been suggested. OBJECTIVES: To determine if postoperative use of an LNG-IUS in women with endometriosis improves pain symptoms associated with menstruation and reduces recurrence compared with treatment with surgery only, placebo or systemic hormones. SEARCH STRATEGY: The following databases were searched: (1) Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials; (2) Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 1); (3) MEDLINE (1966 to January 2006) and EMBASE (1980 to January 2006); (4) National Research Register (NRR). (5) The citation lists of relevant publications, review articles, abstracts of scientific meetings and included studies were also searched. SELECTION CRITERIA: Trials were included if they compared women undergoing any type of surgical treatment for endometriosis with uterine preservation then randomized to LNG-IUS insertion within two to three months versus no treatment, placebo (inert IUD) or systemic treatment. Diagnostic laparoscopy alone was excluded. DATA COLLECTION AND ANALYSIS: Two review authors (AM Abou-Setta and HG Al-Inany) independently selected studies for inclusion and extracted data. Statistical analysis was performed in accordance with the statistical guidelines developed by the Cochrane Menstrual Disorders and Subfertility Group. Data extracted from the trials was analyzed on an intention-to-treat basis. For binary data, the overall common odds ratio (OR) (that is, the odds of having clinical symptoms) and the risk difference with 95% confidence interval (CI) were calculated using the Mantel-Haenszel fixed-effect method. MAIN RESULTS: In one small randomized controlled trial (RCT) there was a statistically significant reduction in the recurrence of painful periods in the LNG-IUS group compared with the control group receiving a gonadotrophin-releasing hormone (GnRH) agonist (OR 0.14, 95% CI = 0.02 to 0.75). The proportion of women who were satisfied with their treatment was higher in the LNG-IUS group than in the control group but this difference did not reach statistical difference (OR 3.00, 0.79 to 11.44). AUTHORS' CONCLUSIONS: One small study has shown that postoperative use of the LNG-IUS reduces the recurrence of painful periods in women who have had surgery for endometriosis. There is a need for further well-designed RCTs of this approach.

Gonadotrophins for idiopathic male factor subfertility.

BACKGROUND: Male factor infertility accounts for 50% of infertility. The treatment of idiopathic male infertility is empirical. Urinary, purified, and recombinant gonadotrophins have been used to improve sperm parameters in idiopathic male infertility with the goal of increasing pregnancy rates. Research addressing pregnancy rates in partners of men treated with gonadotrophins has had conflicting results and needs to be analysed. OBJECTIVES: To determine the effectiveness of gonadotrophin administration to men with idiopathic subfertility on spontaneous pregnancy rate and in assisted reproductive techniques (ARTs). SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (19 November 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, issue 4, 2004), MEDLINE (1966 to April 2005), EMBASE and Biological Abstracts (1980 to November 2004). Searches were not limited by language. The bibliographies of included, excluded trials and abstracts of major meetings were searched for additional trials. Authors and pharmaceutical companies were contacted for missing and unpublished data. SELECTION CRITERIA: Truly randomised controlled trials where gonadotrophins were administered for the treatment of idiopathic male subfertility with reporting of pregnancy rates were included in the review. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. We analysed data regarding pregnancy occurring within 3 months after gonadotrophin therapy. MAIN RESULTS: Four RCTs with 278 participant were included in the analysis. None of the studies had an adequate sample size and they had variable follow-up periods. None of the studies reported live birth or miscarriage rates. Compared to placebo or no treatment, gonadotrophins showed a significantly higher pregnancy rate per couple randomized within 3 months of completing therapy (OR 3.03, 95% CI 1.30 to 7.09). Pregnancy rate was 13.4% (19/142) in the gonadotrophin group and 4.4% (6/136) in the control group. AUTHORS' CONCLUSIONS: The number of trials and participants is insufficient to draw final conclusions. A large multicenter study with adequate power is needed.

Recombinant versus urinary human chorionic gonadotrophin for ovulation induction in assisted conception.

BACKGROUND: For the last few decades urinary human chorionic gonadotrophin has been used to induce final follicular maturation and for triggering ovulation in assisted conception. Recombinant technology has allowed the production of two drugs that can be used for the same purpose: to mimic the endogenous luteinizing hormone (LH) surge. This would allow commercial production to be adjusted according to market requirements. In addition all urinary contaminants would also be removed. Hence, this would allow the safe subcutaneous administration of a compound with less batch-to-batch variation. However, prior to a change in practice, the effectiveness of the recombinant drugs should be known, compared to the currently used urinary human chorionic gonadotrophins. OBJECTIVES: To assess the safety and efficacy of subcutaneous rhCG and high dose rLH compared with intramuscular uhCG for inducing final oocyte maturation and triggering ovulation. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (27 August 2003), the Cochrane Central Register of Controlled Trials (CENTRAL on The Cochrane Library, issue 4, 2003), MEDLINE (1966 to Feb 2004) and EMBASE (1980 to Feb 2004). Searches were not limited by language. The bibliographies of included, excluded trials and abstracts of major meetings were searched for additional trials. Authors and pharmaceutical companies were contacted for missing and unpublished data. SELECTION CRITERIA: Two reviewers independently scanned titles and abstracts, and selected those that appeared relevant for collection of the full paper. Only truly randomised controlled trials comparing rhCG or high dose r-LH with urinary hCG for triggering ovulation in assisted conception for treatment of infertility in normogonadotrophic women were included. DATA COLLECTION AND ANALYSIS: Assessment of inclusion/exclusion, quality assessment and data extraction were performed independently by at least two reviewers. Discrepancies were discussed in the presence of a third reviewer and a consensus reached. Quality assessment included method of randomisation, allocation concealment, blinding of participants and assessors, reporting of a power calculation, intention to treat analysis, and handling of dropouts. Data extraction included characteristics of participants, the intervention and control procedures, and outcomes. MAIN RESULTS: Seven RCTs were identified, four comparing rhCG and uhCG and three comparing rhLH and uhCG. There was no statistically significant difference between rhCG vs uhCG regarding the ongoing pregnancy/ live birth rate (OR 0.98, 95% CI 0.69 to 1.39), pregnancy rate, miscarriage or incidence of OHSS. There was no statistically significant difference between rhLH vs uhCG regarding the ongoing pregnancy/ live birth rate (OR 0.94, 95% CI 0.50 to 1.76), pregnancy rate, miscarriage or incidence of OHSS. The manufacturer of rhLH has decided not to further develop this product. rhCG was associated with a reduction in the incidence of local site reactions and other minor adverse effects (OR 0.47, 95% CI 0.32 to 0.70). AUTHORS' CONCLUSIONS: There is no evidence of difference in clinical outcomes between urinary and recombinant gonadotrophins for induction of final follicular maturation. Additional factors should be considered when choosing gonadotrophin type, including safety, cost and drug availability.

A prospective controlled study of karyotyping for 430 consecutive babies conceived through intracytoplasmic sperm injection.

OBJECTIVE: To compare the karyotype of babies conceived through ICSI with that of naturally conceived babies. DESIGN: Prospective controlled study. SETTING: The Egyptian IVF-ET Center, Cairo, Egypt. PATIENT(S): Four hundred and thirty babies conceived through ICSI and 430 babies conceived naturally. INTERVENTION(S): ICSI and karyotyping. MAIN OUTCOME MEASURE(S): Abnormal karyotype. RESULT(S): Four hundred and thirty consecutive babies conceived through ICSI who were delivered in one hospital had 15 abnormal karyotypes (3.5%). Of the 15 babies, 7 were of female phenotype and 8 of male phenotype. Six babies had sex chromosome anomalies, 8 had autosomal anomalies, and 1 had combined sex chromosome and autosomal anomalies. A control group of 430 consecutive babies conceived naturally who were delivered in one hospital had no abnormal karyotype. The difference between the two groups was significant (P<.001). CONCLUSION(S): ICSI carries a small but significant increased risk of abnormal karyotyping to the offspring. This risk appears to be equally distributed between autosomal and sex chromosome anomalies.

Gonadotrophin-releasing hormone antagonists for assisted conception.

BACKGROUND: Over the last two decades, a long protocol of Gonadotrophin-releasing hormone agonist (GnRHa) to prevent premature LH surges has been the standard treatment for ovarian stimulation in assisted reproduction. In the long protocols (with GnRHa started either in the mid luteal phase or in the early follicular phase of the preceding cycle) gonadotrophin administration is delayed until pituitary desensitization has been achieved, which usually takes 2-3 weeks. Gonadotrophin-releasing hormone antagonists produce immediate suppression of gonadotrophin secretion, hence, they can be given after starting gonadotrophin administration. This will result in dramatic reduction in the duration of treatment cycle and will avoid estrogen deprivation symptoms associated with GnRH agonist induced down-regulation. Assuming comparable clinical outcome, these benefits would justify a change from the standard long protocol of GnRH agonists to the new GnRH antagonist regimens. OBJECTIVES: To compare the efficacy of gonadotrophin-releasing hormone (GnRH) antagonists with the standard long protocol of GnRH agonists for controlled ovarian hyperstimulation in assisted conception. SEARCH STRATEGY: Search strategies included on-line searching of the MEDLINE and EMBASE databases and the Cochrane Menstrual Disorders and Subfertility Group's Specialised Register from 1982 to 2001, and hand searching of bibliographies of relevant publications and reviews, and abstracts of scientific meetings. SELECTION CRITERIA: Only randomised controlled studies comparing different protocols of GnRH antagonists with GnRH agonists in assisted conception cycles were included in this review. DATA COLLECTION AND ANALYSIS: Data were extracted into 2 x 2 tables. For the primary outcomes, clinical pregnancy per woman randomised and prevention of premature LH surge, the overall common odds ratio (OR) and the risk difference with 95% confidence interval (CI) were calculated after verifying the presence of homogeneity of treatment effect across all trials. Secondary outcomes considered were the number of oocytes retrieved, clinical pregnancy per oocyte retrieval and per embryo transfer, spontaneous abortion, incidence of severe ovarian hyperstimulation syndrome and the amount of gonadotrophins used. Where relevant data were missing or unclear the authors were consulted. MAIN RESULTS: Five trials comparing the new fixed protocol of GnRH antagonist to the long protocol of GnRH agonist fulfilled the inclusion criteria and were included. In four studies, the multiple low-dose (0.25 mg) antagonist regimen was applied and in one study, the single high-dose (3 mg) antagonist regimen was investigated. In all trials, reference treatment included a long protocol of GnRHa (buserelin, leuprorelin or triptorelin) starting in the mid-luteal phase of the preceding cycle. In comparison to the long protocol of GnRHa, the overall OR for the prevention of premature LH surges was 1.76 (95% CI 0.75, 4.16), which is not statistically significant. There was a significantly fewer clinical pregnancies in those treated with GnRH antagonists (OR 0.78, 95% CI 0.62, 0.97). The absolute treatment effect (ATE) was calculated to be 5%. The number needed to treat (NNT) was 20. There was a statistically significant reduction in incidence of severe ovarian hyperstimulation syndrome, (RR 0.36, 95% CI 0.16, 0.80) using antagonist regimens as compared to the long GnRHa protocol. REVIEWER'S CONCLUSIONS: The new fixed GnRH antagonist protocol (i.e. with antagonist start fixed on day 6 of gonadotrophin stimulation) is a short and simple protocol with a significant reduction in incidence of severe OHSS but a lower pregnancy rate compared to the GnRH agonist long protocol. There is a non significant difference between both protocols regarding prevention of premature LH surge. The clinical outcome may be further improved by developing more flexible antagonist regimens taking into account individual patient characteristics. The GnRH antagonist flexible regimen should be the area of research in the near future.

Intra-venous albumin for preventing severe ovarian hyperstimulation syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic condition that occurs after the administration of human menopausal gonadotrophin (hMG) with or without gonadotrophin releasing hormone (GnRH) agonists. OHSS is a threat to every woman undergoing ovulation induction and is potentially lethal in its severest form. Severe OHSS is characterised by growth of multiple large follicles with massive extravascular protein rich fluid shift. This may lead to hypovolaemia, haemoconcentration, oliguria, and electrolyte disturbance. Human albumin solutions are now used in the management of shock and other conditions in which restoration of blood volume is urgent, the acute management of burns, and clinical situations associated with hypoproteinaemia. Recently, a number of clinical trials with conflicting results have been reported in which albumin has been tested as a possible way for preventing the severe form of OHSS. OBJECTIVES: To review the effectiveness of human albumin administration in prevention of severe ovarian hyperstimulation syndrome. SEARCH STRATEGY: The Menstrual Disorders and Subfertility Group literature search strategy was used to identify randomised trials that had compared the use of human albumin with placebo or no treatment in the prevention of severe ovarian hyperstimulation syndrome. A diverse search strategy was employed, including handsearching of core journals from 1966 to the present, searching bibliographies of relevant trials, MEDLINE, EMBASE, PsychLIT and CINAHL databases, the MDSG specialised register, abstracts from North American and European meetings and contact with authors of relevant papers. SELECTION CRITERIA: Trials were included if they compared the effect of human albumin with placebo or no treatment on relevant outcomes. Only randomised controlled studies were included in this review. DATA COLLECTION AND ANALYSIS: Trials under consideration were evaluated for methodological quality and appropriateness for inclusion without consideration of their results. Relevant data were extracted independently by two reviewers using the standardized data extraction sheet. Validity was assessed in terms of method of randomization, completeness of follow-up, presence or absence of crossover and co-intervention. DATA SYNTHESIS: 2x2 tables were generated for all relevant outcomes. Odds ratios were calculated using the Peto modified Mantel-Haenszel technique. MAIN RESULTS: Meta-analysis of the three included trials demonstrated significant reduction in severe ovarian hyperstimulation syndrome on administration of human albumin (common odds ratio 0.1, 95% confidence interval 0.03 to 0.39). There was no evidence of an increase in the pregnancy rate (common odds ratio 1.69, 95% confidence interval 0.7 to 4.07). REVIEWER'S CONCLUSIONS: This review shows a clear benefit from administration of intra-venous albumin at the time of oocyte retrieval in prevention of severe OHSS in high-risk cases. However, the results of this review can not be regarded as conclusive as they are based on only three small trials. Further trials are urgently needed.

Intra-venous albumin for preventing severe ovarian hyperstimulation syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic condition that occurs after the administration of human menopausal gonadotrophin (hMG) with or without gonadotrophin releasing hormone (GnRH) agonists. OHSS is a threat to every woman undergoing ovulation induction and is potentially lethal in its severest form. Severe OHSS is characterised by growth of multiple large follicles with massive extravascular protein rich fluid shift. This may lead to hypovolaemia, haemoconcentration, oliguria, and electrolyte disturbance. Human albumin solutions are now used in the management of shock and other conditions in which restoration of blood volume is urgent, the acute management of burns, and clinical situations associated with hypoproteinaemia. Recently, a number of clinical trials with conflicting results have been reported in which albumin has been tested as a possible way for preventing the severe form of OHSS. OBJECTIVES: To review the effectiveness of human albumin administration in prevention of severe ovarian hyperstimulation syndrome. SEARCH STRATEGY: The Menstrual Disorders and Subfertility Group literature search strategy was used to identify randomised trials that had compared the use of human albumin with placebo or no treatment in the prevention of severe ovarian hyperstimulation syndrome. A diverse search strategy was employed, including handsearching of core journals from 1966 to November 2001, searching bibliographies of relevant trials, MEDLINE, EMBASE, PsychLIT and CINAHL databases, the MDSG specialised register, abstracts from North American and European meetings and contact with authors of relevant papers. SELECTION CRITERIA: Trials were included if they compared the effect of human albumin with placebo or no treatment on relevant outcomes. Only randomised controlled studies were included in this review. DATA COLLECTION AND ANALYSIS: Seven randomised controlled trials were identified, five of which met our inclusion criteria and enrolled 378 women (193 in the albumin treated group and 185 in the control group). Trials under consideration were evaluated for methodological quality and appropriateness for inclusion without consideration of their results.The five included trials were single-centre parallel randomised controlled studies. Relevant data were extracted independently by two reviewers using the standardized data extraction sheet. Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention. DATA SYNTHESIS: 2x2 tables were generated for all relevant outcomes. Odds ratios were calculated using the Peto modified Mantel-Haenszel technique. MAIN RESULTS: Meta-analysis of the five included trials demonstrated significant reduction in severe ovarian hyperstimulation syndrome on administration of human albumin (odds ratio was 0.28 (95% CI 0.11 to 0.73). Relative risk was 0.35 (0.14 - 0.87) and absolute risk reduction was 5.5. For every 18 women at risk of severe OHSS, albumin infusion will save one more case. There was no evidence of an increase in the pregnancy rate (odds ratio was 1.09, (95% CI 0.65 to 1.83) REVIEWER'S CONCLUSIONS: This review shows a clear benefit from administration of intra-venous albumin at the time of oocyte retrieval in prevention of severe OHSS in high-risk cases. Whether the NNT would justify the routine use of albumin infusion in cases at risk of severe OHSS needs to be judged by clinical decision makers.

Intrauterine insemination versus fallopian tube sperm perfusion for non tubal infertility.

BACKGROUND: Controlled ovarian hyperstimulation (COH) together with intrauterine insemination (IUI) is commonly offered to couples with infertility factors not involving the fallopian tubes. Intrauterine insemination gained its popularity because it is simple, non-invasive and cost-effective technique. Another simple non invasive method was introduced called fallopian tube sperm perfusion (FSP). This technique was developed to ensure the presence of higher sperm densities in the fallopian tubes at the time of ovulation than standard IUI provides. Fallopian tube sperm perfusion is based on pressure injection of 4 ml of sperm suspension with attempt of sealing of the cervix to prevent semen reflux. The IUI technique on the other hand is based on intrauterine injection of 0.5 ml of sperm suspension without flushing the tubes. A number of randomised controlled trials have been published comparing the efficacy of FSP with standard IUI. There were considerable variations in the results. The aim of this review was to determine whether outcomes differ between FSP and IUI in improving the probability of conception. OBJECTIVES: To investigate whether outcomes differ between fallopian tube sperm perfusion and intrauterine insemination in the treatment of non tubal subfertility resulting in pregnancies and live births. SEARCH STRATEGY: We searched the Menstrual Disorders & Subfertility Group trials register (24 March 2003), MEDLINE (January 1966 to July 2003) and EMBASE (January 1988 to July 2003). Abstracts of the American Society for Reproductive Medicine (1987 to 2003) and European Society for Human Reproduction and Embryology (1987 to 2003) meetings were searched with the same key- or text words. SELECTION CRITERIA: Only randomised controlled studies comparing fallopian tube sperm perfusion with intrauterine insemination were included in this review. The method of allocation was assessed to determine whether each study was truly randomised or pseudo-randomised. Only first period data of cross-over trials were included for analysis. Couples who have been trying to conceive for at least one year were included but only when the female partner had patent tubes. DATA COLLECTION AND ANALYSIS: Two independent reviewers (AC and MJ) selected the trials for inclusion based on the quality of the studies. MAIN RESULTS: Overall six studies involving 474 couples were included in the meta-analysis. Only one study assessed live birth rates (OR 1.17, 95% CI 0.39 3.53). The results for pregnancy rate per couple were statistically significant with FSP showing higher pregnancy rates (OR 1.85, 95% CI 1.23 to 2.79 using the odds ratio with the fixed effect model. To check the results the random effect model was used, which gave a wider confidence interval which crossed the line of no significance (OR 1.76, 95% CI 0.77 to 4.05). As a result, these outcomes should be interpreted with caution. Subgroup analysis revealed that couples suffering from unexplained subfertility benefit from FSP over IUI, resulting in significantly higher pregnancy rates (OR 2.88, 95% CI 1.73 to 4.78). Excluding studies which used the Foley catheter for tubal perfusion resulted in a significant difference favouring FSP for all indications (OR 2.42, 95% CI 1.54 to 3.80). REVIEWERS' CONCLUSIONS: FSP may be more effective for non-tubal subfertility, but the significant heterogeneity should be taken into account. As a result no advice based on the meta-analysis could be given for the treatment of non-tubal subfertility. Subgroup analysis, which did not show evidence of statistical heterogeneity, suggested that couples with unexplained infertility may benefit from FSP over IUI in terms of higher pregnancy rates. FSP may therefore be advised in couples with unexplained subfertility. Results suggested the possibility of differential effectiveness of FSP depending on catheter choice.

Embryo culture media and IVF/ICSI success rates: a systematic review.

BACKGROUND The media that are used to culture human preimplantation embryos are considered to be an important factor for the success rates of IVF/ICSI. Here, we present a systematic review of randomized controlled trials (RCTs) on the effect of culture media on IVF/ICSI success rates. METHODS RCTs published between January 1985 and July 2012 were eligible for inclusion. The primary outcome was live birth. Secondary outcomes were health of babies born, ongoing pregnancies, clinical pregnancies, miscarriages, multiple pregnancies, implantation rate, cryopreservation rate, embryo quality and fertilization rate. For those media that were evaluated in more than one comparison, an unconventional meta-analysis was performed by pooling the data of the media they were compared to. RESULTS Twenty-two RCTs were included that evaluated 31 different comparisons. Conventional meta-analysis was not possible for any of the outcomes as nearly all trials compared different culture media. Only four trials reported on live birth, and one of them reported a significant difference. Nine trials reported on ongoing and/or clinical pregnancy rates, of which four showed a significant difference. Pooling the data did not reveal a superior culture medium. CONCLUSIONS It is yet unknown what culture medium leads to the best success rates in IVF/ICSI. Given the potential importance of culture media for treatment outcome, rigorously designed RCTs are needed for currently available, as well as newly introduced culture media.

Evaluation of the use vs nonuse of urinary catheterization during cesarean delivery: a prospective, multicenter, randomized controlled trial.

OBJECTIVE: To prospectively investigate the effects on urinary tract infection (UTI) of indwelling urinary catheter placement during cesarean delivery. STUDY DESIGN: Randomized controlled trial. RESULT: There were no significant differences between the two groups regarding patient demographics. There was, however, a statistically significant increase in women using general anesthesia in the catheterized group (CG). Even so, the incidence of UTI was significantly greater in the CG (P<0.001). In addition, mean time to patient ambulation, first postoperative voiding, oral rehydration, intestinal movement and duration of hospital stay were significantly less in the uncatheterized group (UG; P<0.001), with most patients (95.3%) self-voiding without any intervention. Moreover, no intraoperative complications were recorded in the UG. CONCLUSION: Non-placement of indwelling urinary catheter during cesarean was more convenient to women with no increase in intraoperative complications, or urinary retention. Indwelling catheter placement in hemodynamically stable patients proved not to be beneficial in this study.

Gonadotrophin-releasing hormone antagonists for assisted conception: a Cochrane review.

Gonadotrophin-releasing hormone (GnRH) antagonists suppress gonadotrophin secretion resulting in dramatic reduction in treatment cycle duration. Assuming comparable clinical outcomes, these benefits may justify changing the standard long GnRH agonist protocol to GnRH antagonist regimens. To evaluate the evidence, databases (e.g. Cochrane Library, MEDLINE, EMBASE) were electronically searched, hand searches were performed, and manufacturers in the field were contacted. Twenty-seven randomized controlled trials (RCT) fulfilled inclusion criteria for comparison of GnRH antagonist with long GnRH agonist protocol. Clinical pregnancy rate and ongoing pregnancy/live-birth rate were significantly lower in the antagonist group (P = 0.009; OR = 0.83, 95% CI 0.72-0.95 and P = 0.02; OR = 0.82, 95% CI 0.68-0.97 respectively). Conversely, incidence of severe OHSS was significantly reduced with the antagonist protocol (P = 0.01; OR = 0.60, 95% CI 0.40-0.88), and interventions to prevent OHSS were administered more frequently in the agonist group (P = 0.03; OR = 0.43, 95% CI 0.20-0.92). Concluding, GnRH antagonist protocols are short, simple, with good clinical outcomes and significant reduction in severe OHSS incidence and gonadotrophin amount; however, the lower pregnancy rate compared with the GnRH agonist long protocol necessitates counselling subfertile couples before recommending change from GnRH agonist to antagonist.

Human albumin is effective in prevention of severe OHSS.

Severe OHSS is an iatrogenic, potentially life-threatening complication of controlled ovarian hyperstimulation. Intravenous human albumin, administered around the time of oocyte retrieval has been claimed to prevent development of this serious event. It was hypothesized that albumin acts through its osmotic pressure and through the binding and inactivation, at a critical time of the cycle, of an hCG-mediated factor secreted by the corpora lutea, that impedes capillary integrity and leads to the development of OHSS. The present article evaluates the available evidence in the medical literature whether albumin is effective in reducing the risk of severe OHSS. Several trials have been identified, most of them were retrospective and few were prospective randomized controlled trials. Although albumin prophylaxis cannot offer absolute protection, all three randomized placebo-controlled trials, that have been published so far, demonstrated a significant reduction in the incidence of severe OHSS.

Intravenous albumin for preventing severe ovarian hyperstimulation syndrome: a Cochrane review.

BACKGROUND: The effectiveness of human albumin administration in prevention of severe ovarian hyperstimulation syndrome (OHSS) was reviewed using the Cochrane Menstrual Disorders and Subfertility Group literature search strategy. METHODS: Only randomized controlled trials (RCT) comparing the effect of human albumin with placebo or no treatment were included in this review. Seven RCT were identified, five of which met our inclusion criteria and enrolled 378 women (193 in the albumin-treated group and 185 in the control group). Trials under consideration were evaluated for methodological quality and appropriateness for inclusion without consideration of their results. The five included trials were single-centre parallel RCT. Relevant data were extracted independently by two reviewers using the standardized data extraction sheet. Validity was assessed in terms of method of randomization, completeness of follow-up, presence or absence of crossover and co-intervention. RESULTS: There was significant reduction in severe OHSS on administration of human albumin [odds ratio (OR): 0.28; 95% confidence interval (95% CI) 0.11-0.73]. Relative risk was 0.35 (95% CI 0.14-0.87) and absolute risk reduction was 5.5. For every 18 women at risk of severe OHSS, albumin infusion will save one more case. There was no evidence of an increase in the pregnancy rate [OR 1.09 (95% CI 0.65-1.83)]. CONCLUSIONS: This Cochrane review shows a clear benefit from administration of i.v. albumin at the time of oocyte retrieval in prevention of severe OHSS in high-risk cases. Whether the number needed to treat would justify the routine use of albumin infusion in cases at risk of severe OHSS needs to be judged by clinical decision-makers.

Intrauterine insemination versus Fallopian tube sperm perfusion in non-tubal subfertility: a systematic review based on a Cochrane review.

BACKGROUND: The objective of this review was to compare the efficacy of Fallopian tube sperm perfusion (FSP) with intrauterine insemination (IUI) in the treatment of non-tubal subfertility. METHODS: The principles of the Cochrane Menstrual Disorders and Subfertility Group were employed. Only randomized controlled studies comparing FSP with IUI were included in this review. The main outcome measures included live birth rates and pregnancy rates per couple. RESULTS: Twenty-eight studies were found performing the comparison of interest. Overall six studies involving 474 couples were included in the meta-analysis. One study only assessed live birth rates, which resulted in no difference in outcome between FSP and IUI [odds ratio (OR) 1.17, 95% confidence interval (CI) 0.39-3.53]. The results in pregnancy rate per couple revealed no statistically significant difference between FSP and IUI (OR 1.76, 95% CI 0.77-4.05). Subgroup analysis revealed that couples suffering from unexplained subfertility clearly benefit from FSP over IUI (OR 2.88, 95% CI 1.73-4.78). Excluding studies which used the Foley catheter for tubal perfusion resulted in a significant difference favouring FSP for all indications (OR 2.42, 95% CI 1.54-3.80). CONCLUSIONS: There is firm evidence that FSP gives rise to higher pregnancy rates in couples with unexplained subfertility and should therefore be advised in these couples. For other indications FSP has not been proven more effective compared with IUI. Results showed that the Foley catheter might not be effective for FSP. Future research should focus on comparing different types of catheters.

A clinicohysteroscopic scoring system of intrauterine adhesions.

We propose a new scoring system for intrauterine adhesions (IUA) that may predict the prognosis after hysteroscopic adhesiolysis. We analyzed hysteroscopic findings and clinical data of patients diagnosed as having IUA by reviewing previously published hysteroscopic classifications of IUA. The data were subjected to evaluation according to the most popular classifications in addition to the proposed classification using a scoring system for different parameters. The results obtained by the proposed scoring system matched well with other classifications regarding grade I and III IUA. But in the cases with moderate IUA (grade II), there was overlap between the classifications (sensitivity 58.3%) which can be attributed to considering the menstrual and reproductive history. Further studies are needed to assess its prognostic value.